Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.
A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.
Bannwart
Linda M
LM
Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
Carter
David S
DS
Cai
Hai-Ying
HY
Choy
Jason C
JC
Greenhouse
Robert
R
Jaime-Figueroa
Saul
S
Iyer
Pravin S
PS
Lin
Clara J
CJ
Lee
Eun Kyung
EK
Lucas
Matthew C
MC
Lynch
Stephen M
SM
Madera
Ann Marie
AM
Moore
Amy
A
Ozboya
Kerem
K
Raptova
Lubica
L
Roetz
Ralf
R
Schoenfeld
Ryan C
RC
Stein
Karin Ann
KA
Steiner
Sandra
S
Villa
Marzia
M
Weikert
Robert J
RJ
Zhai
Yansheng
Y
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013623:Tail / Q000187:drug effects
D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D011759:Pyrrolidines; D012701:Serotonin; D009638:Norepinephrine